Monday, November 19, 2007

A new publication in BMC Bioinformatics by Eppley et al. is available describing Strainer. Strainer is a metagenomics analysis software package focused on population genetics, from the Banfield lab. The software is available here.

Their summary of the software:

Background Metagenomic analyses of microbial communities that are comprehensive enough to provide multiple samples of most loci in the genomes of the dominant organism types will also reveal patterns of genetic variation within natural populations. New bioinformatic tools will enable visualization and comprehensive analysis of this sequence variation and inference of recent evolutionary and ecological processes.

Results We have developed a software package for analysis and visualization of genetic variation in populations and reconstruction of strain variants from otherwise co-assembled sequences. Sequencing reads can be clustered by matching patterns of single nucleotide polymorphisms to generate predicted gene and protein variant sequences, identify conserved intergenic regulatory sequences, and determine the quantity and distribution of recombination events.

Conclusions The Strainer software, a first generation metagenomic bioinformatics tool, facilitates comprehension and analysis of heterogeneity intrinsic in natural communities. The program reveals the degree of clustering among closely related sequence variants and provides a rapid means to generate gene and protein sequences for functional, ecological, and evolutionary analyses.

A new paper on GOLD - the Genomes On Line Database has been published in Nucleic Acids Research. GOLD is an amazing resource for those interested in microbial genomes ... there are so many genome projects out there that it is VERY hard to keep track of them. GOLD does this for you.

Plus it has data organized in nice ways (like by phylogenetic trees) and you can also download all the information. If you want a nice survey of genome projects, check out the statistics page.

Saturday, November 17, 2007

This is a bit late, but I am now giving out my second "Adaptationomics Award" to David Brown, for his article in the Washington Post on "How science is rewriting the book of genes." This award is for somehow misusing genomics to push forward ideas that are excessively adaptationist (i.e., somehow claiming that something must be adaptive simply because it is observed to exist). I have given out one before (see here).

The article by Brown itself reports on some moderately recent changes in human genetics. Among the items discussed are "junk DNA", alternative splicing, and "inefficiencies" in genetic machinery. Some of the discussion in the article in interesting. But it is the last topic, the "inefficiencies" that really gets to me.

It starts off

"It used to be a rule -- actually, more of an assumption -- that the genetic machinery of living organisms was never intentionally wasteful or inaccurate. It turns out this isn't always true, either."

First of all, there is no "intention" in genetic machinery (or by implication, in evolution). I note that this is one of the hallmarks of adaptationism (and adaptationomics) - the anthropomorphizing of DNA.

Then Brown describes some recent papers suggesting that for some protein coding genes, there are (get ready for this) phenotypic differences in alleles that have only synonymous differences. That is, these alleles code for the same protein but use different codons for certain amino acids. Now, never mind that it has been known for 20+ years that codon usage is under selection in some cases (e.g., see papers by HiroshiAkashi such as this one).

What gets me here is that the discussion that centers on the notion that some synonymous differences are either "inefficient" or "wasteful" and that there MUST be an explanation as to why a cell would do this.

He asks

" Why would evolution favor this built-in inefficiency?"

No - nowhere in the discussion has there been any evidence presented that evolution "favors" this kind of thing (by favor, I assume he means something akin to positive selection, but emotions make evolution so much closer no?). So it would be better to ask "Is this under positive selection" or, in emotional terms "Does evolution favor this?"

And the next discussion is even more adaptationistic. Here he discusses "nonsense mediated decay" whereby translation is terminated in the middle of making a protein. Brown then asserts that this wastefulness must have some adaptive explanation. And he does this by a painful analogy:

Think of a cell as containing a factory that makes both tractors and tanks. In peacetime, few tanks are made, but the knowledge and capacity is never lost. Most tanks are built halfway and then broken down, with the parts sent back up the assembly line for reuse.

But then comes great stress; say the cell is experiencing too much heat or not enough oxygen or food. That's where nonsense-mediated decay (NMD) comes into play. It's suddenly wartime, but instead of refitting the factory to make tanks, all the cell has to do is give the order to take the half-made tanks to completion.

Umm -- I do not even know where to begin with this. Is he implying that the ribosome needs to keep its wheels greased in order to know how to make the protein when it is needed? I am not clean. But regardless, the implication is clear --- there MUST be an adaptive explanation for all examples of NMD. Just in case oyu did not see the push for adaptationism --- the end sentence reminds us:

Just the right amount of wrong instructions and wasteful habits -- that's what evolution has built into all of us.

Those interested in the coming personal genomics world should check out Amy Harmon's article in the New York Times. Harmon discusses her own foray into getting sampled herself - a personal story on personal genomics. Oh - so ripe for word play. For a good discussion of the paper and some of the related issues see Matthew Herper's blog here.

I personally think the whole field has rushed a wee bit ahead of the science (which reminds me to point out - if you are looking for a new career, I think genetic/genomic counselor is going to be one of the hottest jobs of the future). But nevertheless, I plan to get tested, so I must not think the science is that off.

Thursday, November 15, 2007

Well, I met Paul Sereno, the dinosaur hunter, for the first time at SciFoo camp (for more about that see here). I confess I was skeptical when he said he was committed to Open Access. But now he has really proven his OA chops. He has a new paper in PLoS One on some friggin cool dinosaur fossils.

I just got in the mail some of the free science education DVDs I ordered from the Howard Hughes Medical Institute. The first one I have looked at is quite good (it is on evolution, of course). I recommend people browse the HHMI catalog here. These could be useful for students as well as for actual courses.

Sunday, November 11, 2007

A big problem these days is the overuse of antibiotics. One of the reasons antibiotics are overused is that people use them for viral illnesses not bacterial ones. But the NY Times Book Review has an example of a "flu virus" that if you have it, you should use antibiotics on. In a review of Craig Venter's new bookin this Sunday's Times, Peter Dizikes refers to one of Venter's achievements in sequencing the first genome:

But he never found a comfortable place in the fledgling government project to chart the human genome and in 1992 joined a new private group, the Institute for Genomic Research. There, Venter and colleagues became the first researchers to chart the whole genome of any organism (the flu virus), among other landmarks, and refined a technique allowing scientists to piece together genomes from small bits of DNA, minimizing the ponderous genetic surveying then in use.

Fine and dandy, except it was not the flu virus, but a bacterium sometimes referred to as H. flu, also known as H. influenzae. It does cause an illness that can resemble the flu, but it is definitely a bacterium. If the Times gets it wrong, one cannot really expect the public to get it right can we? I am not sure what the solution here is, but maybe we should stop saying things are "flu-like" when we mean "flu-like symptoms." Or maybe we need better diagnostics for the home, so that people can figure out what they have more easily.

Saturday, November 10, 2007

There is an article in this Sundays' New York Times by Amy Harmon about prejudice's possibly being revived and stoked by the oncoming personal genomics revolution. I think there is no doubt this is coming. The problem is really two fold in my opinion.

First, as reflected in the story, it is pretty clear that despite the claims of some researchers who seem like they simply want to avoid the subject, we will start to see more findings of genetic differences among populations. . For example, Marc Feldman from Stanford (who by the way was on my thesis committee) is quoted as saying

“There are clear differences between people of different continental ancestries,” said Marcus W. Feldman, a professor of biological sciences at Stanford University

The second part of the problem, in my opinion, is an extension of something I complain about routinely here - the overselling of genomics. In this case we have a double effect. First, is the effect of "DNA." Somehow, when analysis of DNA is part of a study or story, people seem to overestimate its importance. Then comes the genomics-effect. Since genomics is about "all" the DNA, it carries even more weight than normal DNA studies. On the one hand, this is reasonable, as genomics does give a more thorough picture than past genetic studies. But on the other hand, genomics gets oversold as somehow telling the whole story. In this regard I buy the argument in the Harmon story reflected in the quote by David Altschuler that

it is so clear that the economic and social and educational differences have so much more influence than genes. People just somehow fixate on genetics, even if the influence is very small.”

I certainly think personal genomics is going to reveal lots of interesting connections between genes and various phenotypes. But there is no doubt data from personal genomics will lead to the amplification of prejudices and biases already present.

Tuesday, November 06, 2007

While open access to information won’t eliminate the development work, by continuing to limit public access to the information for which the public has paid, we risk losing that vital moment of inspiration which leads to something that makes our lives easier, or healthier, or to a whole new industry. It’s not a risk we can afford to keep taking

There has been lots and lots of talk about "population genomics" in the last few years. For microbes, people have been doing this type of genome wide survey within populations for some time. But for multicellular organisms there have been only a few studies and most of these were limited in scope. Now comes a in depth study of Drosophilasimulans published in PLoS Biology. This project, led by colleagues of mine at UC Davis (David Begun is first author, Chuck Langley is senior author) did "light" whole genome sequencing (at the Washington University Genome Sequencing Center) of seven lines of D. simulans and one line of D. yakuba.

There is lots of interesting population genomics, population genetics and evolutionary analysis in this paper. If anyone out there is interested in personal genomics or human population genomics in any way, it is worth checking out this paper as a model for what can be done in multicellulareukaryotes.

Saturday, November 03, 2007

There is an interesting column on SFGate.com about microbes living in and on people. By Mark Morford, SF Gate Columnist

He talks about eating earthworms as a kid.

Of course, it turns out, biologically speaking, that big, dirty earth-muncher probably did my immune system, my intestinal tract and all the happy bacteria therein a world of good. It's true.

Furthermore he says

we as an overpampered culture are probably not getting enough nasty buggy immune-system-boosting microbes in our diet, in our meats, in our mouths. And therefore we should probably, you know, eat a bit more crap.

I am not sure I would go as far as suggesting eating crap, but I second the notion that we as a society have to stop being obsessed with getting rid of all bacteria. Bacteria are overall good.